Osteoarthritis (OA) affects over 50 million Americans and has a substantial impact on the economy and the health care system. Currently, there is no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. Cartilage degeneration is thought to be the primary pathology associated with the disease. Recent developments in chondro-protective drugs, gene therapy, and the development of biomaterials for cartilage resurfacing have generated substantial demand for noninvasive techniques for detecting changes in cartilage. These developments and any other potential therapies can effectively work only if the disease is detected early. Among the most significant early changes in articular cartilage in OA is the loss of proteoglycans (PG). Conventional MRI techniques, which rely on the T1, T2, proton density, and magnetization transfer (MT) have proven inconclusive in the detection of early biochemical changes in the cartilage. However, these techniques are excellent for detecting the gross tissue morphological changes in the knee joint. A non-invasive assessment of biochemical markers in OA would have a major impact on the ability to make an early and appropriate therapeutic intervention, monitor the clinical outcome, and aid in evaluating new treatment modalities. Recently, we have demonstrated in model systems, ex-vivo and in-vivo pilot studies that the spin-lock MRI can track early biochemical changes in cartilage. In this proposal, we are employing the high-resolution proton T1? relaxation mapping in order to characterize various clinical grades of OA (natural disease) obtained from total knee replacement surgery patients and validating against reference standard sodium MRI. Secondly, we will optimize the high-resolution (spatial and temporal) 3D -T1? relaxation mapping with transmit-receive 8-channel phased array knee coil and parallel imaging (GRAPPA, m-SENSE) at 3T on healthy controls as well as symptomatic subjects in a temporal fashion (0, 6, 12 and 18 months) to determine whether the ex-vivo observations hold true in-vivo situations and correlate with delayed gadolinium enhanced MRI of cartilage (3D-dGEMRIC). The purpose of this proposal is to characterize and identify the role of high-resolution non-invasive MR methods that assess disease risk and progression. Specifically, we will assess whether identified early OA lesions at baseline T1?-MRI examinations are predictive of morphological loss of cartilage over an 18 month period. The novel non-invasive biochemical markers will not only affect our ability to characterize/monitor large OA population in a quantitative manner but also possibly identify patients at risk for rapid progression of disease. Successful completion of proposed work has the potential for defining early biochemical markers that are risk factors and predictors for knee OA progression.